Exposure to indoor environmental contaminants is a major health risk factor, particularly in relation to allergic disease and asthma. In the United States alone, over 50 million people suffer from allergies each year, with an estimated annual cost of over $18 billion. Although numerous contaminants have been identified indoors, mitigation in most cases is possible because their sources, chemical characteristics, dissemination, and health effects have been identified. Contaminants that tend to be particularly challenging to manage are those that either remain un-identified or that we do not fully understand. Bed bugs have resurged globally during the last 20 years, severely affecting the quality of life in disadvantaged communities. I recently discovered and quantified large amounts of histamine in bed bug-infested homes. Although histamine has been extensively investigated as a food contaminant in fish and alcoholic beverages, chronic exposure to histamine has not been considered because histamine has never been detected as a contaminant in homes. Histamine is a downstream modulator in the mammalian immune response, and it is routinely used in provocation tests, including bronchial challenge and skin tests. The presence of large histamine deposits in household dust and its multiple clinical effects (e.g., vasodilation, inflammation, neuromodulation) predict that dermal and respiratory exposure to histamine could constitute a serious health risk. I therefore hypothesize that histamine is ubiquitous in bed bug infested homes, particularly in inner-city low-income residences, and chronic exposure to histamine poses serious health risks to humans. I propose an integrated and interdisciplinary approach to understand the contribution of bed bugs to histamine residues in homes, the pervasiveness and spatial distribution of histamine in the indoor environment, and the effects of histamine on human health. If successful, this project will identify a new environmental contaminant that has gone undetected and unabated for almost two decades. To this end, I will address the following specific aims: 1. Quantify bed bug histamine production and determine the extent of histamine production in other arthropods. 2. Characterize the spatial distribution of histamine in bed bug infested homes. 3. Correlate environmental histamine with the bed bug resurgence and adverse health outcomes 4. Determine the bioactivity and clinical relevance of bed bug derived histamine Presently, no programs offer the opportunity to conduct cutting edge research at the intersection of indoor entomology and public health. Therefore, to address the problems outlined above, I require research independence. This award, supported by significant commitments from my host institution, will provide me with the infrastructure and mentoring to rapidly develop into an independent researcher. I am well-prepared to bypass the traditional post-doctoral phase because of my experience working on projects that span several levels of biological organization, my leadership in international collaborative projects, mentorship of several undergraduate students, strong publication record, and my proven ability to coordinate large-scale multi-disciplinary studies. The experience I have gained and my productivity during my graduate training surpasses what many scientists achieve during the first 3?5 years of post-doctoral training.